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  • Title: Anti-tumour effects of HL-37, a novel anthracene derivative, in-vivo and in-vitro.
    Author: Xie SQ, Hu GQ, Zhang ZQ, Xu M, Ji BS.
    Journal: J Pharm Pharmacol; 2008 Feb; 60(2):213-9. PubMed ID: 18237469.
    Abstract:
    Many anthracene derivatives possess excellent anti-tumour activity and are extensively used clinically as anti-tumour agents. However, their clinical use is frequently limited by emergence of multidrug resistance (MDR) in tumour cells. Therefore, new agents with the ability to overcome MDR are needed for cancer treatment. HL-37, a novel anthracene derivative, exhibited potent anti-cancer activity in both drug-sensitive (K562) and multidrug-resistant (K562/DOX) leukaemia cells. Mechanistically, we found that HL-37 was neither a substrate nor an inhibitor of P-glycoprotein (P-gp) and could overcome apoptotic resistance via up-regulation of p53 protein and down-regulation of Bcl-xL protein. In addition, HL-37 also induced K562/DOX cell apoptosis and a decrease in G(0)/G(1) phase. Moreover, reduction of mitochondrial membrane potential, release of cytochrome c and an increased expression of cleaved protein fragment of caspase-3, caspase-9 and caspase-8 were also observed. Importantly, HL-37 was found to be better tolerated and more effective at inhibiting tumour growth than bisantrene in a xenograft mouse model.
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